Studies in Amide and Peptide Synthesis

酰胺和肽合成研究

• 批准号: 10080734
• 负责人: Jeffrey Nicholas Johnston
• 金额: $ 34.39万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080734
• 关键词: Adopted; Amides; Amidines; Amines; Amino Acids; Benchmarking; Biological; Calorimetry; Carbon; Carboxylic Acids; Catalysis; Chemicals; Complement; Complex; Cyclic Peptides; Development; Esters; Evolution; Excision; Expeditions; Foundations; Glycine; Goals; Halogens; Health; Human; Hydrogen Peroxide; Hydroxylamine; In Situ; Ions; Keto Acids; Laboratories; Life; Ligation; Methods; Molecular Weight; Names; Natural Products; Nature; Nitrogen; Nitrogen Dioxide; Nylons; Organic Chemistry; Outcome; Oxazoles; Peptide Synthesis; Peptides; Pharmacologic Substance; Phase; Physical condensation; Preparation; Process; Pyrrolidines; Reaction; Reaction Time; Reagent; Reporting; Research Personnel; Scheme; Site; Solid; Source; Speed; Stereoisomer; Techniques; Technology; Therapeutic; Therapeutic Uses; Titrations; Triazoles; Tryptophan; Tyrosine; Urea; Water; alkalinity; base; chemical synthesis; cost; drug development; epimerization; improved; innovation; interest; nitroalkane; novel strategies; peptide chemical synthesis; programs; small molecule; tool

4.2.1 Project Summary and Relevance This proposal seeks support to develop a fundamentally new approach to amide and peptide chemical synthesis, one that complements existing methods based on dehydrative amide synthesis using carboxylic acids and amines. Bromonitroalkanes serve as carboxylic acid surrogates in a direct amide synthesis that utilizes an amine acceptor and an activating agent (a halonium ion). The concise preparation of amides derived from nonnatural amino acids, common constituents of biologically active linear and cyclic peptides that have been isolated from natural sources, is a central theme. Without this new paradigm, alternative chemical methods would provide access to the desired amides at rising cost due to the large number of steps required to prepare complex peptides, and the contamination of intermediates and products by stereoisomers that are difficult to remove. The practical chemical synthesis of biologically active peptides is an immediate goal. In the short term, peptides of modest size (~10 residues) will be prepared and diversified. In the long term, this innovative approach to amide synthesis will be used in combination with conventional methods to provide access to large peptides (e.g. biologics) modified site-specifically with nonnatural amino acids.

4.2.1项目总结及相关性